recent multoiple sclerosis article abstracts of interest

[robert miller]

57. Polman CH; Koetsier JC.

      [Copolymer 1 in the treatment of multiple sclerosis].

    Nederlands Tijdschrift voor Geneeskunde, 1994 Dec 31, 138(53):2636-7.

      Language:  Dutch.

          Pub type:  Clinical Trial; Clinical Trial, Phase III; Journal Article;

    Randomized Controlled Trial.



130. Bastianello S; Pozzilli C; D'Andrea F; Millefiorini E; Trojano M; Morino

         S; Gasperini C; Bozzao A; Gallucci M; Andreula C; et al.

       A controlled trial of mitoxantrone in multiple sclerosis: serial MRI

       evaluation at one year.

     Canadian Journal of Neurological Sciences, 1994 Aug, 21(3):266-70.

             Pub type:  Clinical Trial; Journal Article; Multicenter Study;

     Randomized Controlled Trial.



Abstract: We present the results of a randomized double-blinded placebo

    controlled, multicenter trial, of low-dose mitoxantrone (MX), after one

    year, in 25 patients with relapsing-remitting multiple sclerosis, who had

    serial enhanced magnetic resonance imaging (MRI). Treatment groups were

    balanced for age, gender, duration of illness and neurological disability.

    Five of the 13 MX patients and 10 of the 12 placebo patients had

    exacerbations during treatment (p < 0.02). The mean change in the extended

    disability status scale was not significantly different between the MX and

    placebo treatment groups. Serial Gadolinium-DTPA enhanced MRI detected no

    significant difference between the MX treated and placebo groups in the

    mean total number of new, enlarging, or Gadolinium-DTPA enhancing lesions;

    there was a trend toward a reduction of new, enlarging and Gadolinium-DTPA

    enhancing lesions in MX patients. Despite this ameliorating effect, the

    results indicate that serial Gadolinium-DTPA enhanced MRI, performed over

    one year in a limited number of patients, could not provide conclusive

    evidence for a role of MX therapy in relapsing-remitting multiple

    sclerosis.



218. Goodkin DE; Jacobsen DW; Galvez N; Daughtry M; Secic M; Green R.

       Serum cobalamin deficiency is uncommon in multiple sclerosis.

     Archives of Neurology, 1994 Nov, 51(11):1110-4.

       

Abstract: OBJECTIVES: To determine the frequency of serum cobalamin (Cbl)

    deficiency and to clarify the biologic importance of low screening Cbl

    levels in patients with multiple sclerosis (MS) and idiopathic myelopathy

    (MYL). BACKGROUND: A significant association between Cbl metabolism and MS

    has been postulated based on the observations that patients with MS have

    lower serum Cbl levels, higher unsaturated Cbl binding capacities, and a

    higher prevalence of macrocytosis than do normal controls. Whether such

    observations have biologic importance as documented by abnormal

    accumulation of metabolites that would result from Cbl deficiency has not

    yet been determined. METHODS: Serum Cbl and folate levels were determined

    in 208 consecutively evaluated patients seen in an outpatient MS clinic

    setting during a 7-month period. Necessary blood samples were obtained for

    165 of these patients. One hundred twenty-five patients had clinically

    definite MS, 31 had clinically probable MS, and nine had MYL. Serum

    methylmalonic acid (MMA) and homocysteine (HCY) concentrations, which rise

    in biologically severe Cbl deficiency, were subsequently determined in all

    patients whose Cbl levels were lower than 301 pg/mL. RESULTS: A Cbl level

    lower than 301 was found in 32 of 156 patients with either clinically

    definite MS or clinically probable MS but in none of the patients with MYL.

    Elevated MMA or HCY levels were found in seven of 32 patients with either

    clinically definite MS or clinically probable MS, six of whom had an

    elevated HCY level and one of urnal Article; Randomized Controlled Trial.

Abstract: 4-Aminopyridine (4-AP) has a favorable effect on the disability of

    certain patients with MS. We investigated the effect of 4-AP on

    neuropsychological performance in 20 MS patients using a randomized,

    double-blind, placebo-controlled, crossover design. Although there was a

    trend for improved performance with 4-AP for two ofing to a randomized, double-blind,

    double-crossover design. MAIN OUTCOME MEASURES: Neurophysiologic variables

    for nonresponders, neurologic functions and symptoms on a visual analogue

    scale for responders, and side effects for both groups. RESULTS: Toxicity

    profiles of 4-aminopyridine and 3,4-diaminopyridine were different, and

    systemic tolerability was reduced for 3,4-di44(11 Suppl 9):S34-42; discussion S42-3.

              Pub type:  Clinical Trial; Journal Article; Multicenter Study;

     Randomized Controlled Trial.



Abstract: This multicenter, stratified, randomized, placebo-controlled,

    double-blind trial evaluated tizanidine for use in the United States for

    spasticity secondary to MS. The 15-week trial was divided into baseline

    (weeks 0 atnd

    physician/prescribers, but not physician/assessors, gave significantly

    better scores in the overall assessment of efficacy and tolerability. No

    significant differences in other secondary efficacy parameters were noted.

    Adverse events were reported for 66 (61%) of the 109 placebo-treated

    patients and 101 (91%) of the 111 tizanidine-treated patients; 6 (6%) and

    14 aticity f h lgsdu omutilescerss.A
rms smuscle one knee exensrs,

   appying Wartenberg's pendulum test. Blood samples, a clinical assessment

    of muscle tone by the Ashworth scale, and muscle strength by the British

    Medical Research Council scale were obtained concomitantly. Confirmatory

    analysis using the change in the relaxation index (R2 value) 1.5 hours

    after each treatment,ceboontrolled trial of tizanidine in the treatment of

       spasticity caused by multiple sclerosis. United Kingdom Tizanidine Trial

       Group.

     Neurology, 1994 Nov, 44(11 Suppl 9):S70-8.

              Pub type:  Clinical Trial; Journal Article; Multicenter Study;

     Randomized Controlled Trial.



Abstract: Tizanidine was evaluated in a prospective, double-blind, randomized,

     r 

   eas 1 eek aterdisontiutionof herp. A arity of adverse events

    was recordytn agini thee n d rei,dallietae ade e-lad  dfcerf symptomaticttnostc

265. Miller DJ; Sanborn KS; Katzmann JA; Rodriguez M.

       Monoclonal autoantibodies promote central nervous system repair in an

       animal model of multiple sclerosis.

     Journal of Neuroscience, 1994 Oct, 14(10):6230-8.

       Abstract: Susceptible strains of mice infected intracerebrally with Theiler's

    murine encephalomyelitis virus develop a chronic, progressive,

    immune-mediated CNS demyelinating disease similar both pathologically and

    clinically to multiple sclerosis. Previous reports indicated that

    polyclonal immunoglobulins from mice injected with homogenized spinal cord

    promote CNS remyelination when given to SJL/J mice chronically infected

    with Theiler's virus. To explore further both the mechanism(s) and

    potential therapeutic usefulness of antibodies in the treatment of CNS

    demyelinating diseases, we made a panel of monoclonal antibodies derived

    from splenocytes of SJL/J mice injected with homogenized spinal cord, and

    screened them for their autoantigen-binding capability. Monoclonal IgM

    autoantibodies from two clones, designated SCH94.03 and SCH94.32, promoted

    fourfold more CNS remyelination than controls when given to chronically

    infected SJL/J mice. CNS remyelination, assessed morphologically by the

    presence of abnormally thin myelin sheaths relative to axonal diameter,

    correlated with the absence of clinical disease progression. In titration

    experiments, treatment with SCH94.03 and remyelination had a positive

    dose-response relationship, and as little as 10 micrograms of antibody

    promoted remyelination. Both SCH94.03 and SCH94.32 showed multiorgan

    autoreactivity, and recognized both surface and cytoplasmic determinants on

    glial cells. We propose that this model provides a unique system to

    elucidate the mechanism(s) and test the reparative potential of

    autoantibodies in the treatment of CNS injury.



302. Nieves J; Cosman F; Herbert J; Shen V; Lindsay R.

       High prevalence of vitamin D deficiency and reduced bone mass in

       multiple sclerosis.

     Neurology, 1994 Sep, 44(9):1687-92.

      Abstract: BACKGROUND: Female patients with multiple sclerosis (MS) are at risk

    for osteoporosis because of gender, immobility, and corticosteroid use.

    METHODS: Bone mineral density (BMD) was measured by dual x-ray

    absorptiometry in 80 female MS patients admitted to a tertiary care

    hospital. All patients completed a questionnaire that included measurements

    of dietary intake and sunlight exposure. Biochemical indices of bone

    metabolism and turnover were measured in a random sample of 52 patients.

    RESULTS: BMD of the lumbar spine and femoral neck was 1 to 2 SDs lower in

    MS women compared with a healthy reference population. BMD was lower in

    patients with more severe MS. The mean 25(OH)D level of the sample

    population (43 nmol/l) was in the insufficient range, and 12 patients (23%)

    had frank vitamin D deficiency (< 25 nmol/l). BMD and age-related BMD (z

    scores) at all skeletal sites measured were lowest when 25(OH)D levels were

    deficient. Parathyroid hormone (PTH) was frankly elevated in 13% of

    patients. PTH levels were negatively correlated with 25(OH)D levels and

    with BMD. Dietary intake of vitamin D was below the recommended level in

    80% of patients, and 40% reported no weekly sunlight exposure. After

    controlling for age, cumulative steroid use was not a determinant of BMD.

    CONCLUSIONS: BMD was significantly reduced in female MS patients, which

    might increase fracture risk two- to threefold. Vitamin D deficiency with

    secondary hyperparathyroidism is prevalent and is probably a significant

    cause of low BMD in this population. Vitamin D deficiency in the female MS

    patient might be safely and inexpensively corrected by the routine use of

    vitamin D supplements.



312. Polman CH; Koetsier JC.

       Cladribine treatment of multiple sclerosis [letter].

     Lancet, 1994 Aug 20, 344(8921):537; discussion 537-8.

              Pub type:  Letter.



314. Grieb P; Ryba M; Stelmasiak Z; Nowicki J; Solski J; Jakubowska B.

       Cladribine treatment of multiple sclerosis [letter].

     Lancet, 1994 Aug 20, 344(8921):538.

             ct from injury

    cells which they support during development, there should soon be

    opportunities for limiting damage following a variety of insults and for

    rescuing degenerating neurones and glia. The discovery that axon

    regeneration is actively inhibited, perhaps in order to maintain stability

    in the complex systems and circuits that are established during

    developmentain rpair strategy but ta rv pssible to restore complex

    cellular arrangements through cell implantation only. Grafted neurones

    survive, produce appropriate neurotransmitters, form connections and

    restore some behaviours, but their relative inability to grow limits the

    degree of structural and functional repair that can be achieved:

    nevertheless, nerve cell implantation isctile dysfunction (SCI, 14; multiple sclerosis, 7;

    discogenic disease, 6) were evaluated and treated with intracavernous

    PGE-1. An average of 3.2 office sessions were required to learn adequate

    self-injection technique and deeie otmal dosage require. ntil
  dsag frSCmewas 2.5 micrograms and increased in 2.5 micrograms

    increments to a mean maintenance dos of6.micrgrams Quartrlyodaarpisi mcriio pdmen thtbia

 orialevoked potentials. The neurological examination findings together

    with the results of the neurophysiological and cystometric tests suggest

    that erectile dysfunction in multiple sclerosis is due to spinal lesions

    situated proximal to the sacral cord. The feasability of papaverine

    intracorporeal injection therapy for men with multiple sclerososis brains that remyelination can occur

    after the myelin damage. This myelin repair is achieved by

    oligodendrocytes, which are the myelinating cells of the central nervous

    system or by oligodendrocytes precursors still present in adult central

    nervous system. Several recently discovered growth factors can stimulate

    oligodendrocytes precursors migration and proliferation,  Neurology, 1994 Oct41:          Pub type:  Letter.







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